Affiliation:
1. CAS Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory of Natural Medicine of Gansu Province Lanzhou Institute of Chemical Physics Chinese Academy of Sciences (CAS) Lanzhou China
2. University of Chinese Academy of Sciences Beijing China
Abstract
An efficient method for the continuous separation of Voriconazole enantiomers was developed using sulfobutyl ether‐β‐cyclodextrin (SBE‐β‐CD) as a chiral selector in high‐speed countercurrent chromatography (HSCCC) with different types. The separation was performed using a two‐phase solvent system consisting of n‐hexane/ethyl acetate/100 mmol/L phosphate buffer solution (pH = 3.0, containing 50 mmol/L SBE‐β‐CD) (1.5:0.5:2, v/v/v). A fast and predictable scale‐up process was achieved using an analytical DE HSCCC instrument. The optimized parameters were subsequently applied to a preparative Tauto HSCCC instrument, resulting in consistent separation time and enantiomeric purity, with throughput boosted by a remarkable 11‐fold. Preparative HSCCC successfully separated 506 mg of the racemate, delivering enantiomers exceeding 99% purity as confirmed by high‐performance liquid chromatography analysis. This investigation presents an effective methodology for forecasting the HSCCC scale‐up process and attaining continuous separation of chiral drugs.